14-3-3σ expression is associated with poor pathological complete response to neoadjuvant chemotherapy in human breast cancers
14-3-3σ expression is associated with poor pathological complete response to neoadjuvant chemotherapy in human breast cancers
复制标题
DOI：
10.1007/s10549-012-1976-x
复制
发表时间：
2012-07-01
影响因子：
3.8
通讯作者：
Noguchi, Shinzaburo
中科院分区：
文献类型：
--
作者：
Nakamura, Yukiko;Oshima, Kazuteru;Noguchi, Shinzaburo
14-3-3 sigma 是 p53 响应 DNA 损伤而诱导的肿瘤抑制基因，据报道与化疗耐药性相关。本研究的目的是调查人类乳腺癌患者中 14-3-3 sigma 表达是否也与对新辅助化疗（包括紫杉醇和 5-FU/表阿霉素/环磷酰胺 (P-FEC)）的耐药性相关。本研究共纳入 123 例接受新辅助化疗 (P-FEC) 治疗的原发性乳腺癌患者。使用新辅助化疗前获得的肿瘤活检样本进行 14-3-3 sigma 和 p53 的免疫组织化学分析以及 TP53 的直接测序。 38 个肿瘤 (31%) 的 14-3-3 σ 呈阳性。 14-3-3 sigma 表达与 TP53 突变或 p53 表达之间没有显着关联。然而，14-3-3 sigma 表达与 P-FEC 的病理完全缓解 (pCR) 呈显着 (P = 0.009) 负相关，多变量分析表明，只有 14-3-3 sigma (P = 0.015) 和雌激素受体 (P = 0.021) 与 pCR 显着且独立相关。 14-3-3 sigma表达和TP53突变状态的组合对pCR具有附加的负面影响，即14-3-3 sigma阴性/TP53突变肿瘤的pCR率为45.5%，14-3-3 sigma阴性/TP53野生肿瘤的pCR率为24.6%，14-3-3 sigma阳性/TP53突变肿瘤的pCR率为23.1%肿瘤，14-3-3 σ 阳性/TP53 野生肿瘤为 0%。这些结果表明，14-3-3 sigma 表达与 P-FEC 抗性显着相关，并且这种关联独立于其他生物标志物。 14-3-3 sigma 表达和 TP53 突变状态的组合对 P-FEC 的反应具有附加的负面影响。
14-3-3 sigma is a tumor suppressor gene induced by p53 in response to DNA damage and reportedly associated with resistance to chemotherapy. The aim of this study was to investigate whether 14-3-3 sigma expression is also associated with resistance to neoadjuvant chemotherapy consisting of paclitaxel followed by 5-FU/epirubicin/cyclophosphamide (P-FEC) in human breast cancer patients. A total of 123 primary breast cancer patients treated with neoadjuvant chemotherapy (P-FEC) were included in this study. Immunohistochemistry of 14-3-3 sigma and p53 as well as direct sequencing of TP53 were performed using the tumor biopsy samples obtained prior to neoadjuvant chemotherapy. Thirty-eight of the tumors (31%) were positive for 14-3-3 sigma. There was no significant association between 14-3-3 sigma expression and TP53 mutation or p53 expression. However, 14-3-3 sigma expression showed a significantly (P = 0.009) negative association with pathological complete response (pCR) to P-FEC, and multivariate analysis demonstrated that only 14-3-3 sigma (P = 0.015) and estrogen receptor (P = 0.021) were significantly and independently associated with pCR. The combination of 14-3-3 sigma expression and TP53 mutation status had an additive negative effect on pCR, i.e., pCR rates were 45.5% for 14-3-3 sigma negative/TP53 mutant tumors, 24.6% for 14-3-3 sigma negative/TP53 wild tumors, 23.1% for 14-3-3 sigma positive/TP53 mutant tumors, and 0% for 14-3-3 sigma positive/TP53 wild tumors. These results demonstrate that 14-3-3 sigma expression is significantly associated with resistance to P-FEC and this association is independent of other biological markers. The combination of 14-3-3 sigma expression and TP53 mutation status has an additively negative effect on the response to P-FEC.